The Asparaginyl Endopeptidase Legumain Is Essential for Functional Recovery after Spinal Cord Injury in Adult Zebrafish

PLoS ONE, 2014 · DOI: 10.1371/journal.pone.0095098 · Published: April 18, 2014

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Unlike mammals, adult zebrafish can regenerate severed axons and recover locomotor function after spinal cord injury. This study investigates the role of legumain, an enzyme, in this regenerative process. The researchers found that legumain expression is upregulated in neurons and macrophages/microglia after spinal cord injury in zebrafish. This upregulation suggests that legumain is involved in the recovery process. By reducing legumain expression using anti-sense morpholino oligonucleotides, the study demonstrated that legumain is essential for locomotor recovery and axonal regrowth after spinal cord injury in adult zebrafish.

Study Duration

6 weeks

Participants

Adult zebrafish (Danio rerio, male, age .6 months)

Evidence Level

Not specified

Key Findings

1
Legumain expression is upregulated in neurons of regenerative nuclei (NMLF and IMRF) during axon regrowth/sprouting after spinal cord injury.
2
Upregulation of legumain expression is also observed in macrophages/microglia and neurons in the spinal cord caudal to the lesion site after injury.
3
Reducing Legumain expression impairs locomotor recovery and axonal regrowth after spinal cord injury.

Research Summary

This study identifies legumain as an essential component for successful spinal cord regeneration in adult zebrafish after complete spinal cord transection. The researchers found that legumain is upregulated in the NMLF during axon regeneration and in the caudal part of the spinal cord, which provides a permissive environment for regeneration. Knockdown of Legumain expression strongly impaired locomotor recovery and axonal regrowth of brainstem neurons, demonstrating its biological function in regeneration.

Practical Implications

Potential Therapeutic Target

Legumain could be a potential therapeutic target for promoting CNS repair in mammals.

Understanding Regeneration

This study provides insights into the molecular mechanisms underlying successful spinal cord regeneration.

Macrophage/Microglia Activation Marker

Legumain may become a useful early activation marker for macrophages/microglia.

Study Limitations

1
The functions of legumain with different cell types in vitro is hampered by the fact that cultured cells cannot be maintained under acidic conditions.
2
The detailed molecular mechanisms of legumain's functions in macrophages/microglia have remained unclear.
3
Further biochemical studies are needed to elucidate mechanistic features of legumain function to develop potential therapies to promote CNS repair in mammals.

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